Transformation to an aggressive, large cell, high-grade, B-cell lymphoma.
Can occur at any time in the course of CLL.
Occurs in approximately 3 percent of patients at a median of 2 years after diagnosis of CLL.
Can develop in patients who had not received chemotherapy.
Can arise from the original CLL clone.
Chromosomal abnormalities are complex and include:
— del 8p, del 9p, del 11q (11q23), 12(+), del 13q, 14q(+), del 17p, del 20 and/or translocations involving chromosome 12.
— Trisomy 12 and chromosome 11 abnormalities are more frequent.
Higher incidence of P53 mutations at transformation.
Three independent risk factors for transformation identified:
— High-level expression of CD38 by leukemia B cells.
— Absence of leukemia-cell deletion at 13q14.
— Leukemia cell expression of certain IgHV genes, notably IGHV4-39.
Clinical and laboratory features:
— Increased serum lactic acid dehydrogenase activity in approximately 80 percent of patients.
— Rapid lymph node enlargement in approximately 65 percent.
— Fever and/or weight loss in approximately 60 percent.
— Monoclonal gammopathy in approximately 45 percent.
— Extranodal disease in approximately 40 percent.
Not all patients with CLL that have rapid lymph node enlargement have Richter transformation.
Infection with herpes simplex virus can cause acute lymphadenitis.
Occasional cases of Richter transformation have histology resembling that of Hodgkin lymphoma (see Chap. 59), termed Richter syndrome with Hodgkin lymphoma features.
— Richter syndrome with Hodgkin lymphoma features may respond favorably to therapy for Hodgkin lymphoma.
Treatment similar to that of patients with high-grade lymphoma (see Chap. 61).
Encouraging responses have been observed with OFAR regimen (see above).
Median survival is 5 months after transformation.